Project Summary/Abstract Like other mammals, humans are dependent on environmental experiences to program our brains. For most humans, enriched and nurturing experiences provided by caregivers in the sensitive period of infancy provide sufficient stimulation to facilitate the formation of neural connections that further enable adaptive exploration and resilience in response to stress. Infants who experience deprivation in environmental stimulation (ES) and parental nurturance (PN), however, later exhibit aberrations in brain development and behavior. Despite the critical importance of the quantity and quality of caregiving experiences in early life, when the brain is developing most rapidly, we know little about how variations in ES and PN during infancy are selectively related to neural development and to stress-related endocrine function. The goal of this project is to conduct a multimethod assessment of ES and PN that includes naturalistic measurement of infant language exposure (including child-directed speech) and well-validated laboratory-based observations of caregiving behavior to infant distress. Importantly, we will link these measures to infant brain structure and function and endocrine responses to stress. Specifically, we propose to study 50 mother?infant dyads recruited to vary in levels of ES and PN provided to the infant in early life. We will use MRI to examine, for the first time, the specific neural correlates of both ES and PN during infancy. We will also examine infant HPA-axis reactivity and regulation to a stressful interaction in relation to variations in levels of ES and PN. We predict that lower levels of ES will be uniquely associated with reduced total gray matter volume and decreased fractional anisotropy in white matter fascicles responsible for interhemispheric communication and language processing. We also predict that lower levels of PN will be uniquely associated with reduced hippocampal volumes and reduced functional connectivity between emotion regulation regions as well as with greater amygdala activation in response to hearing negative emotional cues (i.e., mother?s angry voice). We predict further that infants who experience lower levels of PN will also exhibit greater HPA-axis reactivity and poorer HPA-axis regulation in response to stress. Findings from this project promise to yield critical insights about the role of early experience in shaping development by elucidating the impact of variations in ES and PN on the developing infant brain and HPA-axis functioning.